Caucasian patients with type 2 diabetes mellitus have elevated levels of monocyte chemoattractant protein-1 that are not influenced by the -2518 A→G promoter polymorphism

• Published in: Diabetes, obesity & metabolism obesity & metabolism, 2005-09, Vol.7 (5), p.570-578
• Main Authors: Zietz, B., Büchler, C., Herfarth, H., Müller-Ladner, U., Spiegel, D., Schölmerich, J., Schäffler, A.
• Format: Article
• Language: English
• Subjects: Aged; Anthropometry; Chemokine CCL2 - blood; Chemokine CCL2 - genetics; Cholesterol - blood; Cytokines - blood; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - genetics; Enzyme-Linked Immunosorbent Assay; European Continental Ancestry Group; Female; Gene Frequency; Genotype; Humans; Insulin - blood; Leptin - blood; Male; MCP-1; Middle Aged; polymorphism; Polymorphism, Genetic; Polymorphism, Restriction Fragment Length; promoter; Promoter Regions, Genetic - genetics; Sex Factors; type 2 diabetes
• ISSN: 1462-8902; 1463-1326
• DOI: 10.1111/j.1463-1326.2004.00436.x

Aim:  To investigate the association of serum levels and the −2518 A→G promoter polymorphism of the gene for chemokine monocyte chemoattractant protein‐1 (MCP‐1), a major chemoattractant of monocytes and activated lymphocytes, with metabolic parameters as well as insulin, leptin and the cytokines tumour necrosis factor‐α (TNF‐α) and interleukin‐6 (IL‐6) in 534 Caucasian patients with type 2 diabetes mellitus. Methods:  MCP‐1 concentrations were measured by enzyme‐linked immunosorbent assay. MCP‐1 genotyping was performed by RFLP analysis in a subset of 426 patients. Results:  Two hundred and thirty‐one (54.2%) patients were homozygous for the wildtype allele (AA), 156 (36.6%) were heterozygous (AG) and 39 (9.2%) were homozygous for the mutated allele (GG). Allelic frequency was similar to non‐diabetic populations (wildtype allele A: 0.73; mutated allele G: 0.27). MCP‐1 mean concentrations and percentiles were substantially higher in non‐diabetic populations but were not influenced by the genotype (AA: 662.0 ± 323.0 pg/ml; AG: 730.6 ± 491.4 pg/ml; GG: 641.2 ± 323.8 pg/ml). MCP‐1 serum levels and genotypes were only marginally related to hormones (insulin and leptin) and cytokines (TNF‐α and IL‐6). Conclusions:  This is the first study providing MCP‐1 levels, percentiles and genotype frequency in a large and representative cohort of patients with type 2 diabetes mellitus. Compared to the literature, MCP‐1 levels were found to be substantially higher in patients with type 2 diabetes mellitus. In contrast, genotype frequencies were similar compared to those in non‐diabetic patients and were not related to MCP‐1 levels. The mechanisms behind these elevated MCP‐1 serum levels in type 2 diabetes are not to be explained by simple associations with hormones, cytokines or genotypes.